Practice 5 structured short- and long-answer medical questions on Weekly Year 2: Cellular Immunology Exam - June 5, 2026 (Sections B & C). Review model answe...
Answer: Dendritic cells (DCs) are professional antigen-presenting cells (APCs) crucial for linking innate and adaptive immunity. Their primary roles include: 1. Antigen capture and processing: DCs efficiently capture antigens in peripheral tissues, process them into peptides, and load them onto MHC class I and II molecules. 2. Migration: Upon antigen capture and maturation (often triggered by PRR signaling), DCs migrate from peripheral tissues to secondary lymphoid organs (e.g., lymph nodes) via afferent lymphatic vessels. 3. T cell activation: In the lymph nodes, DCs present processed antigens (via MHC I and II) to naive T cells. They also provide essential co-stimulatory signals (e.g., B7-CD28 interaction) and secrete cytokines, which are critical for the activation, proliferation, and differentiation of antigen-specific T cells.
Answer: MHC Class I molecules primarily present endogenous antigens, which are peptides derived from proteins synthesized within the cell's cytoplasm (e.g., viral proteins from infected cells, tumor antigens, or self-proteins). These are recognized by CD8+ cytotoxic T lymphocytes (CTLs). MHC Class II molecules primarily present exogenous antigens, which are peptides derived from proteins internalized by endocytosis or phagocytosis from the extracellular environment (e.g., bacterial components, soluble foreign proteins). These are typically recognized by CD4+ helper T lymphocytes.
Answer: T cell activation requires two distinct signals to prevent inappropriate immune responses. Signal 1 is the antigen-specific signal provided by the T cell receptor (TCR) binding to an MHC-peptide complex on an antigen-presenting cell (APC). Signal 2 is the co-stimulatory signal, which is non-antigen specific but crucial. This typically involves the interaction of CD28 on the T cell with B7 molecules (CD80/CD86) on the professional APC. Co-stimulation is vital because it ensures that T cells are only fully activated by APCs that have been appropriately activated (e.g., by pathogens via pattern recognition receptors). Without co-stimulation, T cells receiving only Signal 1 may become anergic (unresponsive) or undergo apoptosis, thereby preventing autoimmune responses against self-antigens presented in the absence of danger signals.
Answer: Natural Killer (NK) cells are a type of lymphocyte belonging to the innate immune system. Key features include: 1. Lack of TCR/BCR: Unlike T and B cells, NK cells do not express antigen-specific T cell receptors or B cell receptors. 2. Rapid response: They can act quickly without prior sensitization or clonal expansion. 3. MHC-independent killing: They do not require MHC presentation to recognize target cells. Their effector functions primarily involve: 1. Cytotoxicity: Direct killing of virally infected cells and tumor cells through the release of perforin and granzymes, which induce apoptosis in target cells. NK cell activity is regulated by a balance of activating receptors (recognizing stress-induced ligands) and inhibitory receptors (recognizing MHC class I molecules on healthy cells, preventing self-attack). 2. Cytokine production: They secrete cytokines such as IFN-γ, which activates macrophages and enhances adaptive immune responses.
Answer: T cell development is a highly regulated process occurring primarily in the thymus, converting hematopoietic progenitor cells into mature, functional, and self-tolerant T lymphocytes. This journey involves several stages of differentiation and critical selection processes. **1. Entry and Early Thymocyte Development (Cortex):** Precursor T cells, originating from the bone marrow, enter the thymus and are initially termed thymocytes. In the outer cortex, these cells are "double negative" (DN), lacking expression of CD4 and CD8 co-receptors. They undergo significant proliferation and initiate T cell receptor (TCR) gene rearrangement. Successful rearrangement of the TCR beta chain leads to its expression with a surrogate alpha chain (pre-TCR), which signals further development. This crucial checkpoint ensures a functional beta chain. Following successful pre-TCR signaling, thymocytes become "double positive" (DP), co-expressing both CD4 and CD8, and then commence TCR alpha chain rearrangement. **2. Positive Selection (Cortex):** DP thymocytes, now expressing a complete TCR, migrate deeper into the thymic cortex. Here, they interact with cortical thymic epithelial cells (cTECs), which express self-MHC class I and II molecules loaded with self-peptides. The purpose of positive selection is to ensure that the newly formed TCRs can functionally recognize self-MHC molecules. Only those thymocytes whose TCRs bind with low-to-intermediate affinity to either self-MHC I or self-MHC II receive survival signals. Thymocytes whose TCRs fail to bind or bind too weakly undergo apoptosis, a process known as "death by neglect." This ensures MHC restriction. Depending on which MHC molecule the TCR binds to, the thymocyte then commits to either the CD4 or CD8 lineage: if the TCR binds to MHC I, the cell downregulates CD4 and becomes a CD8+ single positive (SP) cell; if it binds to MHC II, it downregulates CD8 and becomes a CD4+ SP cell. **3. Negative Selection (Cortex-Medulla Junction & Medulla):** Single positive thymocytes then migrate to the medulla. Here, they encounter medullary thymic epithelial cells (mTECs) and dendritic cells, which present a diverse array of self-peptides, including tissue-specific antigens (TSAs) expressed under the control of the Autoimmune Regulator (AIRE) gene. The purpose of negative selection is to eliminate potentially autoreactive T cells. Thymocytes whose TCRs bind with high affinity to self-MHC-peptide complexes receive strong apoptotic signals, leading to their death. This process is crucial for establishing central self-tolerance, preventing the mature T cell repertoire from attacking the body's own tissues. A small proportion of self-reactive CD4+ T cells that survive negative selection may differentiate into regulatory T cells (Tregs), which play a role in peripheral tolerance. **4. Exit from Thymus:** Thymocytes that successfully navigate both positive and negative selection mature into naive, immunocompetent CD4+ or CD8+ SP T cells. These cells are then released from the thymus and circulate through secondary lymphoid organs, ready to encounter foreign antigens and participate in adaptive immune responses. In summary, T cell development in the thymus meticulously crafts a functional and safe T cell repertoire. Positive selection ensures the T cells are MHC-restricted and capable of recognizing antigen, while negative selection eliminates self-reactive T cells, thereby preventing autoimmunity and guaranteeing self-tolerance.